5-(1-isobutyl-1H-pyrazol-4-yl)-6-isopropyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile

ID: ALA3785443

PubChem CID: 90454779

Max Phase: Preclinical

Molecular Formula: C17H20N6O

Molecular Weight: 324.39

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)Cn1cc(-c2[nH]c3c(C#N)cnn3c(=O)c2C(C)C)cn1

Standard InChI:  InChI=1S/C17H20N6O/c1-10(2)8-22-9-13(7-19-22)15-14(11(3)4)17(24)23-16(21-15)12(5-18)6-20-23/h6-7,9-11,21H,8H2,1-4H3

Standard InChI Key:  NVCPEMIYZIDHEV-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 24 26  0  0  0  0  0  0  0  0999 V2000
   -1.0028   -1.5132    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0028    1.5132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3155    0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3155   -0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2917   -0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2917    0.7475    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7138    1.2033    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.5889    0.0182    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7138   -1.2033    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1825   -2.6263    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5579   -3.7661    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9991    2.7132    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6217    1.4865    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6560    0.8780    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6319    2.6865    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6168   -1.4950    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9669   -0.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.9732   -1.9832    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2262   -3.2840    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7582   -2.9755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8359   -4.6526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9548   -5.8675    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4431   -6.9637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7613   -5.7427    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  6  2  1  0
  5  1  1  0
  1  4  1  0
  3  2  1  0
  3  4  2  0
  5  6  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9  5  2  0
  9 10  1  0
 10 11  3  0
  2 12  2  0
  3 13  1  0
 13 14  1  0
 13 15  1  0
  4 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  1  0
 20 16  2  0
 19 21  1  0
 21 22  1  0
 22 23  1  0
 22 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3785443

   5-[1-(2-methylpropyl)pyrazol-4-yl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 324.39

Molecular Weight (Monoisotopic): 324.1699

AlogP: 2.54

#Rotatable Bonds: 4

Polar Surface Area: 91.77

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.41

CX Basic pKa: 1.66

CX LogP: 2.06

CX LogD: 2.06

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.80

Np Likeness Score: -1.30

References

1. McAllister TE, England KS, Hopkinson RJ, Brennan PE, Kawamura A, Schofield CJ..  (2016)  Recent Progress in Histone Demethylase Inhibitors.,  59  (4): [PMID:26710088] [10.1021/acs.jmedchem.5b01758]

2. Sayegh, Joyce J and 9 more authors.  2013-03-29  Identification of small molecule inhibitors of Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase by a sensitive high throughput screen.  [PMID:23408432]

3. England, Katherine S and 12 more authors.  2014-12-01  Optimisation of a triazolopyridine based histone demethylase inhibitor yields a potent and selective KDM2A (FBXL11) inhibitor.  [PMID:26682034]

4. Korczynska, Magdalena M and 14 more authors.  2016-02-25  Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors.  [PMID:26699912]

5. Labadie, Sharada S SS and 19 more authors.  2016-09-15  Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.  [PMID:27499454]

6. Horton, John R and 21 more authors.  2018-04-12  Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A.  [PMID:29537847]

7. Horton, John R and 22 more authors.  2018-12-13  Structure-Based Engineering of Irreversible Inhibitors against Histone Lysine Demethylase KDM5A.  [PMID:30392349]

8. Jaikhan, Pattaporn P and 5 more authors.  2019-05-15  Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors.  [PMID:30928196]

9. Zhao, Bing and 8 more authors.  2020-04-15  Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B).  [PMID:32155529]

Source

Source(1):

• Scientific Literature